Dermatologically active ingredients for topical application to human skin are often insoluble solids (also called particulates) in media that are acceptable for skin application, e.g. without limitation, benzoyl peroxide (“BPO”), and insoluble antifungals. In order to prepare these topical products, dermatologically active ingredients are often suspended in the vehicle, which may be, for example without limitation, gels, creams, or lotions.
It is also desirable to have these types of dermatologically active ingredients placed on pads for delivery by wiping the pad on the skin. Pads may additionally be disposable for both convenience and sanitary reasons. However, several problems exist with this approach when it is applied to dermatologically active ingredients that are insoluble, minimally or weakly soluble.
First, the dermatologically active ingredient compositions, e.g. without limitation, BPO compositions, are not uniformly deposited on the pad. Second, the dermatologically active ingredient composition are not uniformly deposited on the skin during the wiping of the pad across the skin. Without uniformity, one cannot predict how much and whether any of the dermatologically active ingredient is delivered, and therefore, the delivery method is ineffective. Specified uniformity is preferred in most drug delivery systems.
Factors that are relevant to these problems include, that a portion of the liquid composition may preferentially squeeze through the fibers of the pad, leaving a high concentration of particulate dermatologically active ingredients on a surface of the pad. On the other hand, dermatologically active ingredient particles may preferentially squeeze through the fibers and leave particles on the walls of the container or in some parts of the pad or container, but not others.
Additionally, the container for a BPO pad, for example, may contribute to these problems. If the container is sealed with an alkaline based adhesive, BPO, a strong oxidizing agent, dissolves the adhesive after being in contact with BPO for as little as a month. The adhesive seal degrades and the two halves of the pouch come apart. Thus, there is also a need for a leak-proof container.
The use of pads stored in jars or large containers to apply single-phase solutions of dermatologically active ingredients has long been known as an effective technique. Because the dermatologically active ingredient is in solution, it remains acceptably distributed throughout the solvent vehicle, and is not susceptible to removal from the solution by filtration or adsorption by the pad.
The use of pads to apply single-phase suspensions of dermatologically active ingredients has been unsuccessful. The suspended dermatologically active ingredient tends to settle to the bottom of the container, resulting in unacceptable variations in dermatologically active ingredient concentration. This problem is aggravated by the tendency of pads to filter out or adsorb the suspended dermatologically active ingredient. Thus, even if the dermatologically active ingredient does not settle out of suspension, it can be collected on the pads unevenly. To make matters worse, having filtered or adsorbed the dermatologically active ingredient out of suspension, such pads have a tendency to retain the dermatologically active ingredient and not release it to the skin.
Oil-in-water and water-in-oil emulsions (e.g. without limitation creams and lotions) have been used as delivery vehicles for suspensions of dermatologically active ingredients (e.g. TRIAZ® of Medicis Pharmaceutical Corp. of Arizona) and work well when used alone as delivery vehicles. These creams and lotions hold the dermatologically active ingredients in suspension fairly well, resulting in even distribution of the dermatologically active ingredient throughout the vehicle, and thus on the skin.
However, when pads or pledgets are used to topically apply creams or lotions, several problems have been encountered. Creams have been found to adhere poorly to pads, and adhere all too well to the pad's container. Attempts to use pads as a delivery vehicle have resulted in the pads being used to wipe or scrape the cream or lotion off the container's walls so that it can be applied to the skin, and often the cream is incompletely released from the pad resulting in under-application of the dermatologically active ingredients. This has been a source of great frustration in the drug delivery art, as pads are a highly desirably method of topical application. For example, in the field of acne treatments, pads have been used for decades to apply solutions of salicylic acid (e.g. Stri-Dex® of Blistex Inc. of Illinois). On the other hand, benzoyl peroxide, which has been known for decades as a superior treatment for acne, has never been successfully marketed with a pad delivery system because it is not soluble and is delivered as a suspension in a cream or lotion. Thus, there is a great and long-standing demand for a way to topically deliver particle suspension of dermatologically active ingredients by way of a pad.